Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12017411 Health-related quality of life associated with irritable bowel syndrome: comparison with o 2002 Apr BACKGROUND: Despite the rapidly growing body of literature on health-related quality of life (HRQoL). placing the results in a context that is meaningful to clinicians and patients is often overlooked. OBJECTIVE: This study sought to quantify the impact of irritable bowel syndrome (IBS) on HRQoL by comparing the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) scores of IBS patients with normative US data and with the scores of patients having other chronic gastrointestinal (GI) and non-GI disorders. METHODS: Two IBS reference groups were identified from the published literature: a largely untreated community sample of health maintenance organization (HMO) members (N = 92) and a sample of patients with IBS recruited through clinics and in the community (N = 140). SF-36 scores for these groups were compared with published US population norms (N = 2474) and with published scores for 3 other IBS samples (N = 464); a sample with other chronic GI disorders (dyspepsia [N = 126], gastroesophageal reflux disease [GERD] [N = 516]); and samples with other chronic episodic disorders (asthma [N = 375], migraine [N = 303], panic disorder [N = 73], rheumatoid arthritis [N = 693]). RESULTS: The scores of patients in both IBS reference groups were significantly lower on several SF-36 domains than those of the US normative population (P < 0.003). Scores on several SF-36 scales were also significantly lower in the IBS reference groups compared with the GERD, asthma, and migraine samples (P < 0.003). Depending on the IBS sample used, scores did not differ or were higher compared with those in the sample with dyspepsia. Relative to the samples with panic disorder and rheumatoid arthritis, the IBS groups had significantly higher scores on most SF-36 domains (P < 0.003). Scores for the HMO reference group were generally higher than those for the clinic/community reference group. CONCLUSIONS: Based on the results of this analysis, IBS is associated with impairment of HRQoL relative to US population norms and to populations with GERD, asthma, or migraine. HRQoL appears to be greater in patients with IBS than in those with panic disorder or rheumatoid arthritis, although the relative symptom severity in these samples was not known.
12942545 Downregulation of a rheumatoid arthritis-related antigen (RA-A47) by ra-a47 antisense olig 2003 Oct Previously we have shown that the expression of RA-A47 (rheumatoid arthritis-related antigen) which is identical to HSP47, a collagen-binding chaperon, is downregulated in chondrocytes by tumor necrosis factor alpha (TNFalpha). RA-A47 was also found on the surface of chondrocytes where it is recognized as an antigen in the serum of rheumatoid arthritis (RA) patients. Its translocation to the cell surface from endoplasmic reticulum membrane where it is normally located was also enhanced by TNFalpha. To understand the significance of RA-A47 downregulation in chondrocytes independent from other effects of TNFalpha, we used an antisense oligonucleotide approach and investigated the effect of this treatment on the expression of molecules related to matrix degradation and production of growth factors for chondrocytic, endothelial, and synovial cells. Here we show that treatment of rabbit chondrocyes and human chondrosarcoma cells HCS-2/8 by ra-a47 antisense S-oligonucleotides significantly reduced the expression of ra-a47 both at mRNA and protein level. Interestingly, this TNFalpha-independent RA-A47 downregulation was associated with a strong induction of matrix metalloproteinase (MMP)-9 mRNA and inducible NO synthase (iNOS) mRNA. The induction of active-type MMP-9 was further detected by gelatin zymography. Under the same conditions, the release of basic fibroblast growth factor (bFGF) and connective tissue growth factor (CTGF) from HCS-2/8 cells into the conditioned medium (CM) was strongly enhanced. These effects were not a result of TNFalpha upregulation, since the ra-a47 antisense oligonucleotide treatment did not enhance TNFalpha synthesis. These observations indicate that downregulation of RA-A47 induces TNFalpha-independent cartilage-degrading pathways involving iNOS and MMP-9. Furthermore, the stimulation of bFGF and CTGF release from chondrocytes may stimulate the proliferation of adjacent endothelial and/or synovial cells.
12370259 A point mutation of Tyr-759 in interleukin 6 family cytokine receptor subunit gp130 causes 2002 Oct 7 We generated a mouse line in which the src homology 2 domain-bearing protein tyrosine phosphatase (SHP)-2 binding site of gp130, tyrosine 759, was mutated to phenylalanine (gp130(F759/F759)). The gp130(F759/F759) mice developed rheumatoid arthritis (RA)-like joint disease. The disease was accompanied by autoantibody production and accumulated memory/activated T cells and myeloid cells. Before the disease onset, the T cells were hyperresponsive and thymic selection and peripheral clonal deletion were impaired. The inhibitory effect of IL-6 on Fas ligand expression during activation-induced cell death (AICD) was augmented in gp130(F759/F759) T cells in a manner dependent on the tyrosine residues of gp130 required for signal transducer and activator of transcription 3 activation. Finally, we showed that disease development was dependent on lymphocytes. These results provide evidence that a point mutation of a cytokine receptor has the potential to induce autoimmune disease.
14660270 Etanercept therapy in patients with autoimmunity and hepatitis C. 2003 Dec Accumulated data suggest that etanercept may be a therapeutic option in patients with hepatitis C and coexisting autoimmune disorders such as rheumatoid arthritis, psoriasis, psoriatic arthritis and ankylosing spondylitis. Additionally, etanercept may actually be of benefit, when used in combination with standard treatments, for hepatitis C.
12056294 Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrex 2002 Apr OBJECTIVE: To evaluate impairment of lung function as an adverse effect associated with methotrexate therapy in patients with juvenile idiopathic arthritis (JIA). METHODS: We performed pulmonary function testing including diffusion capacity for carbon monoxide as measured by the single breath method (DLCO-SB) in 89 children with juvenile idiopathic arthritis. Forty (45%) were treated with methotrexate for a median of 24 months (range 3 to 120 months). Except for the presence of asthma in two children, there was no clinical or radiological evidence of pulmonary disease. RESULTS: Pulmonary function testing demonstrated moderate airway obstruction in two children with known bronchial asthma. Neither obstructive nor restrictive alteration of ventilation was found in any other patient. Two juvenile idiopathic arthritis patients showed a reduced CO diffusion capacity of 64 and 67%. One of them was treated with methotrexate. CONCLUSIONS: With regard to lung function impairment treatment with low dose methotrexate appears to be safe even when performed for several years reaching a total amount of up to 3.5 g. In contrast to studies performed in adult rheumatoid arthritis patients, in children with juvenile idiopathic arthritis impairment of lung function is a rare event.
12688106 Isolation of Chlamydia trachomatis or Ureaplasma urealyticum from the synovial fluid of pa 2003 Jan BACKGROUND: The aim of this study was to contribute to the insight of the role of the infectious agent in ethiopathogenesis of the Reiter's syndrome development, which could directly influence the choice of treatment of these patients. METHODS: Eighteen patients with urogenital form of the Reiter's syndrome and 16 controls (6 with rheumatoid arthritis and 10 with pigmented villonodular synovitis) were included in the study. In all patients standard laboratory analyses of the blood, urine and stool were made; antibody titer to Chlamydia trachomatis and Ureaplasma urealyticum was determined in synovial fluid and serum; isolation of Chlamydia trachomatis and Ureaplasma urealyticum in urethral, cervical and conjunctival swabs, as well as in prostatic and synovial fluid, was also made. HLA typing was done, too. Chlamydia was isolated in the McCoy cell culture treated with cycloheximide, while Ureaplasma was identified according to its biochemical properties grown on cell-free liquid medium. RESULTS: Chlamydia trachomatis was isolated from the synovial fluid of 4 patients with Reiter's syndrome (22.2%), while Ureaplasma urealyticum was isolated in 7 of them (38.9%). These microorganisms were not found in any synovial fluid of the control group patients. CONCLUSION: Presence of these bacteria in the inflamed joint might be an important factor in etiopathogenesis of this disease, and it supports the hypothesis that arthritis in Reiter's syndrome is probably of the infectious origin.
12517251 Novel therapies for the treatment of juvenile rheumatoid arthritis (juvenile idiopathic ar 2003 Jan The majority of children with juvenile idiopathic arthritis respond well to conventional treatment. However, some children will have a more aggressive disease course and will be resistant to standard management. Over the past 20 years, growth in our understanding of the immunopathogenesis of juvenile idiopathic arthritis and related diseases has facilitated significant therapeutic advances. In this report, recently released antirheumatic drugs, as well as some treatments currently in development, will be discussed. Biological agents, such as antiTNF and other cytokines inhibitors, and unique drugs, such as thalidomide, provide new opportunities to suppress the inflammation found in severe cases of systemic onset juvenile idiopathic arthritis and can obtain a satisfactory outcome.
15327561 Successful treatment of severe psoriasis and psoriatic arthritis with adalimumab. 2004 Aug Adalimumab, a fully human-derived recombinant monoclonal antibody against tumour necrosis factor-alpha, has been shown to be effective for the treatment of patients with moderately to severely active rheumatoid arthritis. We report two patients with long-standing recalcitrant psoriasis and psoriatic arthritis who, after multiple treatment failures with conventional and experimental antipsoriatic medications, both responded to treatment with adalimumab. Significant clinical improvement was noted in both skin and joint disease in the two patients after several weeks of treatment with adalimumab. We are unaware of previous published reports of adalimumab therapy in patients with psoriasis and psoriatic arthritis.
17041384 Myasthenia gravis in a patient with pauciarticular juvenile chronic arthritis. 2002 Oct There have been reported cases of children with histories of pauciarticular juvenile chronic arthritis (JCA) later developing myasthenia gravis (MG) as young adults. This is intriguing because it had been considered rare to diagnose a second autoimmune disease in a patient with pauciarticular JCA, unlike in those with adult-onset rheumatoid arthritis. We report a case of MG in a 20-year-old woman with a history of pauciarticular JCA. She presented with bilateral ptosis, weakness, and a history of dysphagia. The diagnosis was confirmed with positive serum acetylcholine receptor antibodies (2000 nm/L) and electromyography showing a decremental response to repetitive muscle stimulation. The patient's inflammatory arthritis was quiescent at diagnosis. The patient underwent a surgical thymectomy and was treated with pyridostigmine, intravenous immunoglobulin, and corticosteroids with a fluctuating clinical course. Previous cases have been reported of MG associated with this subtype of JCA, suggesting a connection in autoimmune pathology. The earlier recognition and management of MG in a patient with pauciarticular JCA presenting with weakness may improve the prognosis of this disease.
15474233 Miscellaneous conditions about the elbow in athletes. 2004 Oct This article reviews some of the conditions about the elbow in athletes or active individuals. The conditions discussed are synovial plica of elbow, radiocapitellar arthritis, congenital dislocation of the radial head, radio-ulnar synostosis, hemophilia and rheumatoid arthritis. In the past, people who had these conditions were instructed to avoid athletic activities; however, they are now being counseled to remain active and to try to exercise on a regular basis.
12022324 Osteopenia in adults with a history of juvenile rheumatoid arthritis. A population based s 2002 May OBJECTIVE: To determine the extent of osteopenia in a population based cohort of adults with a history of juvenile rheumatoid arthritis (JRA). METHODS: The Rochester Epidemiology Project database was used to identify all cases of JRA diagnosed among Rochester, Minnesota residents under the age of 16 years between January 1, 1960, and December 31, 1993. Thirty-two of the 57 adult patients in this population based cohort (ages 19-53 years, mean 35) participated in this study. Average length of followup from the time of diagnosis was 27.1 years (median 26.9, range 7.7-39.1). Dual energy x-ray absorptiometry scans were used to assess bone density of the lumbar spine, hip, distal one-third radius, and whole body. In addition, a number of variables that influence bone mass were analyzed. RESULTS: Although many participants had T scores within the normal range (T score > -1) at all measured sites, 41% (n = 13) were osteopenic (T score < or = -1) at either the lumbar spine or femoral neck. Twenty-eight percent (n = 9) had T scores < or = -1 in the lumbar spine (p = 0.058 relative to expected). Thirty-two percent (n = 10) had T scores < or = -1 in the femoral neck (p = 0.012 relative to expected). Several variables were significantly (p < 0.05) associated with low bone density in this cohort of adults with a history of JRA, including: (1) revised Steinbrocker functional class > or = 2 during adolescence, indicating poorer physical functioning; (2) lack of participation in organized sports during adolescence (a surrogate measure of physical activity); (3) tobacco use during adolescence; and (4) lower calcium intake during adolescence. CONCLUSION: Although many adults with a history of JRA have normal bone density, a substantial subset are osteopenic, placing them at increased risk of fractures later in life. This observation is particularly striking given the predominance of patients with pauciarticular JRA in this population based group. We identified several variables associated with osteopenia in this cohort. Further work is needed to identify those patients with JRA who may benefit from aggressive therapy targeted at preventing the longterm morbidity associated with osteopenia.
14994400 Reactive arthritis following an outbreak of Campylobacter jejuni infection. 2004 Mar OBJECTIVE: To study the occurrence and the clinical picture of musculoskeletal (MSK) complications including reactive arthritis (ReA) following an outbreak of Campylobacter jejuni. METHODS: An outbreak of C. jejuni infection occurred in 2000 in Asikkala, Finland, during which 350 exposed subjects contacted the Municipal Health Centre (MHC). All primary care physicians in the MHC were advised to refer patients with acute MSK complications to the Rheumatism Foundation Hospital (RFH) for a specialist clinical examination, which was performed
15182255 Circulating cytokines in primary Sjögren's syndrome determined by a multiplex cytokine ar 2004 Jun Plasma cytokines play an important role in the pathogenesis of Sjögren's syndrome (SS) by initiating and perpetuating various cellular and humoural autoimmune processes. The aim of the present study was to describe a broad spectrum of T-cell and B-cell cytokines, growth factors, chemokines and molecules that could contribute to cell death in SS. A novel protein array system was utilized to measure simultaneously the levels of 25 plasma cytokines of patients with primary SS and healthy individuals. Furthermore, we correlated these plasma cytokine levels with potential laboratory and clinical parameters related to disease activity in SS. A subset of plasma cytokines [e.g. interleukin-1beta (IL-1beta), IL-6, CXCL8 (IL-8), IL-12 p40, IL-15, tumour necrosis factor-alpha (TNF-alpha), epidermal growth factor, CCL4 (MIP-1beta), CCL2 (MCP-1), CCL11 (Eotaxin), CCL5 (RANTES), TNF-RI and TNF-RII] was found to significantly differ between patients and controls. Also, distinct populations of cytokines were found to differentiate between patients with normal versus elevated ESR or IgG levels and patients with the presence or absence of extra-glandular manifestations (EGMs). Our results support the assumption that the multiplex cytokine array system can be successfully utilized in the diagnosis and disease management of SS. Furthermore, it may provide a powerful tool in the design of individualized anticytokine therapies.
12737332 Bone marrow findings in patients with adult Still's disease. 2003 OBJECTIVE: Peripheral neutrophilia is one of characteristic laboratory findings in patients with adult Still's disease (ASD). We performed this study to identify the bone marrow findings in patients ASD. METHODS: We examined 12 bone marrow biopsy specimens from patients with ASD. RESULTS: The most frequent finding was granulocyte hyperplasia (12/12, 100%) and hypercellularity was observed in 75.0% (8/12) of patients. Plasmacytosis was present in 8.3% (1/12) of specimens. Histiocytosis and reactive hemophagocytosis were found in 25.0% (4/12) and in 16.7% (2/12) respectively. CONCLUSION: Our results show that bone marrow granulocyte hyperplasia is the main possible mechanism for peripheral neutrophilia and that histiocytic activation is a not infrequent bone marrow findings in patients with ASD.
11851084 [Severe hypokalemia with paralysis in a patient with distal renal tubular acidosis as an i 2002 Feb 2 In a 33-year-old woman with a recent flaccid paralysis of the arms and legs, laboratory tests demonstrated a severe hypokalemia with hyperchloremic metabolic acidosis and abnormally acidified urine. The urinary anion gap was positive in the presence of acidosis, thus establishing the diagnosis of distal renal tubular acidosis. The patient made a full recovery after potassium and alkali replacement. Further investigation revealed Sjögren's syndrome as the underlying cause.
15513685 Long-term follow-up study of pulmonary findings in patients with primary Sjögren's syndro 2004 BACKGROUND: In a previous study pulmonary hyperinflation was observed frequently in patients with primary Sjogren's syndrome (pSS) and elevated serum beta-2 microglobulin (beta2m) concentrations were associated with hyperinflation. OBJECTIVE: To evaluate the significance of baseline serum beta2m concentration and to identify other possible risk factors for pulmonary involvement in long-term follow-up of patients with pSS. METHODS: Nineteen pSS patients whose pulmonary function tests (PFTs) had been previously studied were reexamined after a median follow-up of 10 years. Pulmonary symptoms were recorded, chest radiograph, and high-resolution computed tomography (HRCT) were evaluated and methacholine provocation and PFTs including flow-volume spirometry, body plethysmography, and diffusing capacity performed. RESULTS: Baseline serum beta2m concentrations correlated inversely with follow-up total lung capacity (TLC), vital capacity (VC), and diffusing capacity (DL), and positively with residual volume (RV), all expressed as percentage of predicted values. Diminished airways resistance (Raw) and, correspondingly, elevated specific conductance (SGaw) were frequent findings in pSS patients at follow-up, indirectly implying stiffness of the lungs and a restrictive decrease in lung volumes. Baseline serum protein concentration was higher and IgG concentration tended to be higher in pSS patients who at follow-up had elevated SGaw compared with others. Interstitial changes in HRCT were found more frequently in patients with elevated SGaw than in those without. CONCLUSION: Our results suggest that subtle restrictive changes in pulmonary function are more prone to develop in the long term in pSS patients with elevated serum beta2m concentration and other signs of immunological activity at baseline.
15124941 Estimating the prevalence among Caucasian women of primary Sjögren's syndrome in two gene 2004 OBJECTIVE: To establish the prevalence among women of primary Sjögren's syndrome (PSS) in Birmingham, UK. METHODS: Eight hundred and forty-six female Caucasians from two general practitioner lists were invited to complete a questionnaire that included a screening question on dry eyes and mouth. Individuals who responded positively were evaluated further. RESULTS: Overall, 65/% of individuals who were sent a questionnaire responded. Two had possible PSS, but were negative for anti-Ro/La antibodies. Our estimates of the prevalence of PSS ranged from < 0.1% up to 0.4%, depending on the assumptions used. CONCLUSION: Our data support previous studies suggesting a prevalence of PSS in the community of 0.1-0.6% rather than those suggesting a higher figure.
12453311 Genetic aspects of Sjögren's syndrome. 2002 Sjögren's syndrome is a multisystem inflammatory rheumatic disease that is classified into primary and secondary forms, with cardinal features in the eye (keratoconjunctivitis sicca) and mouth (xerostomia). The aetiology behind this autoimmune exocrinopathy is probably multifactorial and influenced by genetic as well as by environmental factors that are as yet unknown. A genetic predisposition to Sjögren's syndrome has been suggested on the basis of familial aggregation, animal models and candidate gene association studies. Recent advances in molecular and genetic methodologies should further our understanding of this complex disease. The present review synthesizes the current state of genetics in Sjögren's syndrome.
12431170 The role of parotid biopsy in the diagnosis of pediatric Sjögren syndrome. 2002 Nov OBJECTIVES: To describe our experience with primary and secondary Sjögren syndrome (SS) in the pediatric population and to evaluate the effectiveness of parotid gland biopsy in the diagnosis of pediatric SS. DESIGN: Case series review of 6 pediatric patients evaluated during a 4-year period with varied head and neck manifestations of SS. SETTING: Tertiary care children's hospital. PATIENTS: Six children (4 boys and 2 girls) ranging in age from 6 to 12 years, who were diagnosed as having primary or secondary SS. INTERVENTION: Six minor salivary gland and 4 parotid gland biopsies for pathologic examination. MAIN OUTCOME MEASURES: Pathologic examination of salivary tissue consistent with SS. RESULTS: All 6 patients underwent minor salivary gland biopsy, 2 (33%) were consistent with SS, while the remaining 4 (67%) were nondiagnostic. The 4 patients with nondiagnostic minor salivary gland biopsy results went on to have parotid biopsies, of which all 4 had histologic findings consistent with SS. No complications were encountered. CONCLUSION: Parotid gland biopsy is an effective and safe means of obtaining salivary gland tissue for histologic evaluation of SS in the pediatric population.
12014215 Acute acalculous cholecystitis associated with systemic lupus erythematosus with Sjogren's 2002 Mar Both systemic lupus erythematosus and Sjogren's syndrome are autoimmune diseases. Almost all organs can be involved but the gall bladder is an unusual site. We report a 39-year-old woman with systemic lupus erythematosus and Sjogren's syndrome presenting with acute acalculous cholecystitis. It is a very rare complication and, in the literature review, surgical interventions are mostly applied for treatment. In our case, high dose corticosteroid was tried and clinical manifestations and radiologic findings were improved.